The role of the fibrous protein spectrin in regulating human red blood cell integrity, elasticity and surface antigen topography will be investigated. To determine how spectrin regulates the distribution of other membrane proteins, the self-assembly properties of isolated spectrin molecules in their various aggregation states will be studied by electron microscopy, optical diffraction and X-ray diffraction of fibers, tactoids and gels. Immunochemical labelling will be used to correlate the distribution of spectrin on the cytoplasmic surface of the erythrocyte membrane with the distribution of intramembranous particles before and after their aggregation by pH, Ca ions or protamine sulfate treatment. As a measure of the control of mobility of other membrane components by spectrin, a novel fluorescence bleaching technique will be used to visualize the rate of diffusion of membrane surface macromolecules. The molecular association between spectrin and other membrane components will be elucidated by reassociating intact spectrin, peptide fragments of spectrin and chemically modified spectrin fragments with spectrin-depleted erythrocyte vesicles under a variety of conditions. It is expected that this detailed examination of the structure and associative properties of the spectrin molecule will provide a firm basis for understanding several pathological syndromes of the red cell which have been traced to perturbations in the organization of its membrane.